1150617-53-0Relevant articles and documents
Fragment Based Optimization of Metabotropic Glutamate Receptor 2 (mGluR2) Positive Allosteric Modulators in the Absence of Structural Information
Szabó, Gy?rgy,Túrós, Gy?rgy I.,Kolok, Sándor,Vastag, Mónika,Sánta, Zsuzsanna,Dékány, Miklós,Lévay, Gy?rgy I.,Greiner, István,Natsumi, Minami,Tatsuya, Watanabe,Keseru, Gy?rgy M.
, p. 234 - 246 (2019/01/15)
Metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAMs) have been implicated as potential pharmacotherapy for psychiatric conditions. Screening our corporate compound deck, we identified a benzotriazole fragment (4) that was rapidly optimized to a potent and metabolically stable early lead (16). The highly lipophilic character of 16, together with its limited solubility, permeability, and high protein binding, however, did not allow reaching of the proof of concept in vivo. Since further attempts on the optimization of druglike properties were unsuccessful, the original hit 4 has been revisited and was optimized following the principles of fragment based drug discovery (FBDD). Lacking structural information on the receptor-ligand complex, we implemented a group efficiency (GE) based strategy and identified a new fragment like lead (60) with more balanced profile. Significant improvement achieved on the druglike properties nominated the compound for in vivo proof of concept studies that revealed the chemotype being a promising PAM lead targeting mGluR2 receptors.
METALLO-BETA-LACTAMASE INHIBITORS
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Page/Page column 78, (2017/04/04)
The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.
Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent γ-Secretase Modulators
Bischoff, Francois,Berthelot, Didier,De Cleyn, Michel,MacDonald, Gregor,Minne, Garrett,Oehlrich, Daniel,Pieters, Serge,Surkyn, Michel,Trabanco, Andres A.,Tresadern, Gary,Van Brandt, Sven,Velter, Ingrid,Zaja, Mirko,Borghys, Herman,Masungi, Chantal,Mercken, Marc,Gijsen, Harrie J. M.
, p. 9089 - 9106,18 (2020/10/15)
The design and the synthesis of several chemical subclasses of imidazole containing γ-secretase modulators (GSMs) is described. Conformational restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in vivo p
NOVEL SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS GAMMA SECRETASE MODULATORS
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Page/Page column 67, (2010/08/18)
The present invention is concerned with substituted bicyclic heterocyclic compounds of Formula (I) wherein Het1, Het2, A1, A2, A3 and A4 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.
NOVEL SUBSTITUTED BENZOXAZOLE, BENZIMIDAZOLE, OXAZOLOPYRIDINE AND IMIDAZOPYRIDINE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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Page/Page column 64, (2010/09/17)
The present invention is concerned with novel substituted benzoxazole, benzimidazole, oxazolopyridine and imidazopyridine derivatives of Formula (I) wherein R1, R2, R3, R4, X, A1, A2, A3, A4, Y1, Y2, Y3 and Z have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.